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Treatments used today cure about 8 out of 10 cases of Hodgkin lymphoma (HL). Still, important research is going on in many university hospitals, medical centers, and other institutions around the world. Scientists are getting closer to finding out what causes the disease and how to better treat it. This is of special interest for hard-to-treat cases, like those that don't respond to current treatments or come back after treatment. Doctors are also looking for ways to limit the long-term side effects linked to HL treatment.
PET/CT scans are commonly used to help doctors stage HL and decide how much treatment needs to be given. Doctors are also looking at whether PET/CT scans done during treatment can help decide if more or less treatment is needed.
Researchers are trying to find out if MRI scans might work as well in children and teens with HL. If so, it would mean less radiation exposure and the resulting long-term side effects in young people.
Overall cure rates for HL are high, but long-term side effects of treatment are an important issue. A very active area of research is directed at learning which patients can be treated with gentler therapy and which patients need stronger treatment.
Doctors are looking to see which patients (especially children) might do just as well with lower doses of radiation, or even no radiation . They're also studying if newer forms of radiation therapy, such as intensity-modulated radiation therapy (IMRT) and proton therapy, might be useful for HL. These approaches focus radiation more precisely on tumors, which limits the doses reaching nearby normal tissues.
A related area of research is finding less-toxic treatments that have fewer serious long-term side effects, yet still cure as many patients as possible. Lower doses of chemotherapy (chemo), as well as new chemo drugs and drug combinations are being studied. Many of these drugs are already used to treat other cancers and have shown promise against HL that has come back (relapsed) after other chemo treatments. Studies are in progress to see if these drugs could work better than the ones now in use.
Doctors are also looking for better chemo drugs to use with stem cell transplant. Again, improving outcomes while limiting long-term side effects is the goal.
Another approach is using newer drugs that better target HL cells. Some of these are described below.
Newer drugs that work differently from standard chemo drugs are now being studied. Researchers are learning a lot about the gene changes found in HL cells. This could lead to drugs that target these changes and spare normal cells. These are known as targeted therapy drugs. Many other types of cancer are already treated with targeted therapies.
Some of these targeted drugs are being studied in combinations, in the hope that they might work better when given together. Many are given along with other cancer treatments, like chemo and/or radiation.
Immunotherapy is treatment that helps the body’s immune system find and attack cancer cells. Immunotherapy is helpful against several types of cancer, including Hodgkin lymphoma.
Immune system cells normally have substances on them that act as checkpoints to keep them from attacking healthy cells in the body. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Today, drugs that block these checkpoints are used to treat HL after other treatments have been tried. Researchers are now studying other ways to use these drugs. For instance, they're looking at whether these drugs might be used as "maintenance therapy" to keep HL from coming back after transplant. They're also testing them as a first treatment for HL. The use of immune checkpoint inhibitors in children and teens, as well as in older people who are too sick to get standard treatment, is also being studied. Several other checkpoint inhibitor drugs are being studied, too.
In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab so they have receptors called chimeric antigen receptors, or CARs on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The altered T cells are then multiplied in the lab and put back into the patient’s blood. They can then find the lymphoma cells and launch a precise immune attack against them.
This technique has shown encouraging results in early clinical trials against some hard-to-treat Hodgkin lymphomas. Doctors are still improving how they make the T cells and are learning the best ways to use them. CAR T-cell therapy is only available in clinical trials at this time.
Monoclonal antibodies (mAbs) are man-made versions of immune system proteins. Some can kill cancer cells by themselves. Others have radioactive molecules or cell poisons attached to them, which help kill cancer cells. An advantage of these drugs is that they seem to target lymphoma cells while having fewer side effects than standard chemo drugs. They may be used alone or along with chemo.
Some mAbs, such as brentuximab vedotin (Adcetris) and rituximab (Rituxan), are already being used to treat some cases of HL. Researchers are now studying if these drugs might be useful in other ways. For instance, brentuximab is now being studied to see if it might be helpful earlier in the course of the disease or as part of the treatment used to get ready for a transplant. And studies are now being done to see if rituximab can help treat classic forms of HL as well as the nodular lymphocyte-predominant type. Researchers are also looking for the best way to use mAbs along with standard treatment. Many newer mAbs are now being studied, too.
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Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-319.
Mata E, Díaz-López A, Martín-Moreno AM, et al. Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets. Oncotarget. 2017;8(67):111386-111395.
Nieto Y, Thall PF, Ma J, et al. Phase II Trial of High-Dose Gemcitabine/Busulfan/Melphalan with Autologous Stem-Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin's Lymphoma. Biol Blood Marrow Transplant. 2018 Mar 1.
Regacini R, Puchnick A, Luisi FAV, Lederman HM. Can diffusion-weighted whole-body MRI replace contrast-enhanced CT for initial staging of Hodgkin lymphoma in children and adolescents? Pediatr Radiol. 2018 Jan 23.
Watkins MP, Fanale MA, Bartlett NL. SOHO State of the Art Updates and Next Questions: Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18(2):81-90.
Last Revised: May 1, 2018
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